Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus.

ABSTRACT: Neuroinflammation is a key component of virtually all neurodegenerative diseases, preceding neuronal loss and associating directly with cognitive impairment. Neuroinflammatory signals can originate and be amplified at barrier tissues such as brain vasculature, surrounding meninges and the choroid plexus. We designed a high content screening system to target inflammation in human brain-derived cells of the blood-brain barrier (pericytes and endothelial cells) to identify inflammatory modifiers. Screening an FDA-approved drug library we identify digoxin and lanatoside C, members of the cardiac glycoside family, as inflammatory-modulating drugs that work in blood-brain barrier cells. An ex vivo assay of leptomeningeal and choroid plexus explants confirm that these drugs maintain their functio

SUBMITTER: Jansson D 

PROVIDER: S-EPMC7910294 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature